Changes in metabolism during toxicity tests.
1. During rodent chronic toxicity studies metabolism may vary according to the age of the animal, or as a result of the effect of the chemical on its own metabolism, or as a result of the toxic properties of the chemical. 2. Foetal and newborn animals are lacking in many, but not all, metabolic enzymes and during the first 30 days of life there is differential development of these enzymes to adult levels. Thereafter activity may remain relatively constant, continue to increase or alternatively decline, occasionally to negligible levels. Typically, metabolism studies used for registration of new pesticides or for evaluation of industrial chemicals are conducted in young adult animals where most enzyme systems are fully developed. 3. At present there are no regulatory requirements for monitoring metabolism during chronic toxicity studies of these two groups of chemicals. Nevertheless, in selected cases monitoring of changes during such studies can be of value in understanding the mechanism of toxicity and the effects observed. 4. Parameters to be studied are discussed, and specific examples are given of the consequences of metabolic changes on the subsequent development of tumours.
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ICI Central Toxicology Laboratory, Macclesfield, Cheshire, UK.
D000367:Age Factors; D000818:Animals; D015197:Carcinogenicity Tests; D006224:Cricetinae; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D008752:Methylene Chloride / Q000378:metabolism / Q000633:toxicity; D051379:Mice; D051381:Rats; D013045:Species Specificity; D015262:Xenobiotics / Q000378:metabolism / Q000633:toxicity*
D015262:Xenobiotics; D008752:Methylene Chloride; D003577:Cytochrome P-450 Enzyme System; D005978:Glutathione